Ab initio molecular orbital study of the structures of purine hydrates

The structures of the isomers of purine hydrates [4(5)-hydroxy-5(4)-hydropurines] have been geometry optimized with ab initio quantum chemical methods at the 6-31G* basis set and with the semiempirical method PM3. These hydrates which can result from reduction of radical species formed by attack of hydroxyl radical at the 4,5 double bond in the purines, show significant geometrical distortion when compared to the natural bases. More specifically, the cis isomers adopt a ''butterfly'' conformation, while in the trans isomers, the pyrimidine and imidazole rings tilt opposite to each other. Our results predict the cis purine hydrate isomers are far more stable than the trans isomers by 10-18 kcal/mol at the 6-31G* level, whereas the 4-hydroxy-5-hydropurines are found to be slightly more energetically stable than the 5-hydroxy-4-hydropurines. The ''butterfly'' conformation of the cis isomers constitutes a bulky lesion which will result in a significant distortion of the DNA helix.